PCYT2 (phosphate cytidylyltransferase 2, ethanolamine) catalyzes the second step in phosphatidylethanolamine (PE) synthesis via the CDP-ethanolamine pathway 1. As a rate-limiting enzyme in PE biosynthesis, PCYT2 produces CDP-ethanolamine, which is coupled with diacylglycerols to form PE 2. PE is a dominant inner-leaflet phospholipid critical for membrane stability, cell division, apoptosis, and immune signaling 34. Mechanistically, PCYT2-synthesized PE regulates multiple cellular processes: it coordinates CXCR5 surface expression for T follicular helper cell differentiation 4, suppresses epithelial-mesenchymal transition in colorectal cancer by elevating YAP1 phosphorylation 5, and maintains mitochondrial function 6. PCYT2 activity declines in aging muscle and during liver regeneration, where downregulation protects against injury 78. Clinically, PCYT2 deficiency causes spastic paraplegia 82 with severe disease manifestations including failure to thrive and progressive muscle weakness 7. PCYT2 knockout mice recapitulate these phenotypes with accelerated aging and bioenergetic impairment. AAV-mediated PCYT2 delivery ameliorates muscle weakness in both disease models and age-related decline 7. Dysregulation of PCYT2-mediated lipid metabolism also associates with disease pathogenesis in hypertriglyceridemia-associated acute pancreatitis and hepatocellular carcinoma 96.